Corticotherapy for traumatic brain-injured Patients - The Corti-TC trial: study protocol for a randomized controlled trial

Trials

The Corti-TC trial group¹  Véronique Sebille¹  Antoine Roquilly¹  Karim Asehnoune¹ 

[1] The Corti-TC trial group

关键词: intensive care unit;    nosocomial infection;    pneumonia;    mineralocorticoid;    glucocorticoid;    corticosteroid insufficiency;    Traumatic brain injury;    Trauma;   

Others  :  1095808
DOI  :  10.1186/1745-6215-12-228

 received in 2011-09-26, accepted in 2011-10-14,  发布年份 2011

【 摘 要 】

Background

Traumatic brain injury (TBI) is a main cause of severe prolonged disability of young patients. Hospital acquired pneumonia (HAP) add to the morbidity and mortality of traumatic brain-injured patients. In one study, hydrocortisone for treatment of traumatic-induced corticosteroid insufficiency (CI) in multiple injured patients has prevented HAP, particularly in the sub-group of patients with severe TBI. Fludrocortisone is recommended in severe brain-injured patients suffering from acute subarachnoid hemorrhage. Whether an association of hydrocortisone with fludrocortisone protects from HAP and improves neurological recovery is uncertain. The aim of the current study is to compare corticotherapy to placebo for TBI patients with CI.

Methods

The CORTI-TC (Corticotherapy in traumatic brain-injured patients) trial is a multicenter, randomized, placebo controlled, double-blind, two-arms study. Three hundred and seventy six patients hospitalized in Intensive Care Unit with a severe traumatic brain injury (Glasgow Coma Scale ≤ 8) are randomized in the first 24 hours following trauma to hydrocortisone (200 mg.day^-1 for 7 days, 100 mg on days 8-9 and 50 mg on day-10) with fludrocortisone (50 μg for 10 days) or double placebo. The treatment is stopped if patients have an appropriate adrenal response. The primary endpoint is HAP on day-28. The endpoint of the ancillary study is the neurological status on 6 and 12 months.

Discussion

The CORTI-TC trial is the first randomized controlled trial powered to investigate whether hydrocortisone with fludrocortisone in TBI patients with CI prevent HAP and improve long term recovery.

Trial registration

NCT01093261

【 授权许可】

   
2011 Asehnoune; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Pelosi P, Ferguson ND, Frutos-Vivar F, Anzueto A, Putensen C, Raymondos K, Apezteguía C, Desmery P, Hurtado J, Abroug F, Elizalde J, Tomicic V, Cakar N, González M, Arabi Y, Moreno R, Esteban A, for the Ventila Study Group: Management and outcome of mechanically ventilated neurologic patients. Critical Care Medicine 2011, 39:1482-1492.
• [2]Seguin P, Tanguy ML, Laviolle B, Tirel O, MalleDant Y: Effect of oropharyngeal decontamination by povidone-iodine on ventilator-associated pneumonia in patients with head trauma. Critical Care Medicine 2006, 34:1514-1519.
• [3]Lepelletier D, Roquilly A, Demeure dit latte D, Mahe PJ, Loutrel O, Champin P, Corvec S, Naux E, Pinaud M, Lejus C, Asehnoune K: Retrospective analysis of the risk factors and pathogens associated with early-onset ventilator-associated pneumonia in surgical-ICU head-trauma patients. J Neurosurg Anesthesiol 2010, 22:32-37.
• [4]Bronchard R, Albaladejo P, Brezac G, Geffroy A, Seince PF, Morris W, Branger C, Marty J: Early onset pneumonia: risk factors and consequences in head trauma patients. Anesthesiology 2004, 100:234-239.
• [5]Osborn TM, Tracy JK, Dunne JR, Pasquale M, Napolitano LM: Epidemiology of sepsis in patients with traumatic injury. Critical Care Medicine 2004, 32:2234-2240.
• [6]Rincón-Ferrari MD, Flores-Cordero JM, Leal-Noval SR, Murillo-Cabezas F, Cayuelas A, Muñoz-Sánchez MA, Sánchez-Olmedo JI: Impact of ventilator-associated pneumonia in patients with severe head injury. The Journal of Trauma: Injury, Infection, and Critical Care 2004, 57:1234-1240.
• [7]Czaja AS, Rivara FP, Wang J, Koepsell T, Nathens AB, Jurkovich GJ, Mackenzie E: Late outcomes of trauma patients with infections during index hospitalization. J Trauma 2009, 67:805-814.
• [8]Safdar N, Dezfulian C, Collard HR, Saint S: Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Critical Care Medicine 2005, 33:2184-2193.
• [9]Hoen S, Asehnoune K, Brailly-Tabard S, Mazoit JX, Benhamou D, Moine P, Edouard A: Cortisol response to corticotropin stimulation in trauma patients: influence of hemorrhagic shock. Anesthesiology 2002, 97:807-813.
• [10]Roquilly A, Mahe PJ, Seguin P, Guitton C, Floch H, Tellier AC, Merson L, Renard B, Malledant Y, Lfet L, Sebille V, Volteau C, Masson D, Nguyen JM, Lejus C, Asehnoune K: Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study. JAMA 2011, 305:1201-1209.
• [11]Cohan P, Wang C, Mcarthur DL, Cook SW, Dusick JR, Armin B, Swerdloff R, Vespa P, Muizelaar JP, Cryer JG, Christenson PD, Kelly DF: Acute secondary adrenal insufficiency after traumatic brain injury: A prospective study. Critical Care Medicine 2005, 33:2358-2366.
• [12]Woiciechowsky C, Schöning B, Lanksch WR, Volk HD, Döcke WD: Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. J Mol Med 1999, 77:769-780.
• [13]Annane D, Sébille V, Charpentier C, Bollaert PE, François B, Korach JM, Capellier G, Cohen Y, Azoulay E, Toché G, Chaumet-Riffaud P, Bellissant E: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002, 288:862-871.
• [14]Bederson JB, Connolly ES, Batjer HH, Dacey RG, Dion JE, Diringer MN, Duldner JE, Harbaugh RE, Patel AB, Rosenwasser RH, American Heart Association: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 2009, 40:994-1025.
• [15]Sartorius D, Le Manach Y, David JS, Rancurel E, Smail N, Thicoïpé M, Wiel E, Ricard-Hibon A, Berthier F, Geugniaud PY, Riou B: Mechanism, Glasgow Coma Scale, Age, and Arterial Pressure (MGAP): A new simple prehospital triage score to predict mortality in trauma patients. Critical Care Medicine 2010, 38:831-837.
• [16]Fine J, Gray R: A proportional hazards model for the subdistribution of a competing risk. J Am Statist Assoc 1999, 94:496-509.
• [17]Keh D, Boehnke T, Weber-Cartens S, Schulz C, Ahlers O, Bercker S, Holk HD, Doecke WD, Falke KJ, Gerlach H: Immunologic and hemodynamic effects of "low-dose" hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. American Journal of Respiratory and Critical Care Medicine 2003, 167:512-520.
• [18]Confalonieri M, Urbino R, Potena A, Piatella M, Parigi P, Pussio G, Porta RD, Giogio C, Blasi F, Umberger R, Meduri GU: Hydrocortisone Infusion for Severe Community-acquired Pneumonia: A Preliminary Randomized Study. American Journal of Respiratory and Critical Care Medicine 2004, 171:242-248.
• [19]Marik PE: Critical Illness-Related Corticosteroid Insufficiency. Chest 2009, 135:181-193.
• [20]Klompas M: The paradox of ventilator-associated pneumonia prevention measures. Crit Care 2009, 13:315. BioMed Central Full Text
• [21]Bandiera GW, Hillers TK, White F: Evaluating programs to prevent unintentional trauma in Canada: challenges and directions. The Journal of Trauma: Injury, Infection, and Critical Care 1999, 47:932-936.
• [22]Snijders D, Daniels JMA, De Graaff CS, Der Werf Van TS, Boersma WG: Efficacy of Corticosteroids in Community-acquired Pneumonia: A Randomized Double-Blinded Clinical Trial. American Journal of Respiratory and Critical Care Medicine 2010, 181:975-982.
• [23]American Thoracic Society, Infectious Diseases Society of America: Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. American Journal of Respiratory and Critical Care Medicine 2005, 171:388-416.
• [24]Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons: Guidelines for the management of severe traumatic brain injury. J Neurotrauma 2007, 24(Suppl 1):S1-106.
• [25]Terragni PP, Antonelli M, Fumagalli R, Faggiano C, Berardino M, Pallavicini FB, Miletto A, Mangione S, Sinardi AU, Pastorelli M, Vivaldi N, Pasetto A, Rocca GD, Urbino R, Filippini C, Pagano E, Evangelista A, Ciccone G, Mascia L, Ranieria M: Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: a randomized controlled trial. JAMA 2010, 303:1483-1489.
• [26]Den Berghe Van G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R: Intensive insulin therapy in the medical ICU. N Engl J Med 2006, 354:449-461.
• [27]NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY-S, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hebert PC, Heritier S, Heyland DH, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ: Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009, 360:1283-1297.
• [28]Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R, Keh D, Kupfer Y, Oppert M, Meduri GU: Corticosteroids in the Treatment of Severe Sepsis and Septic Shock in Adults: A Systematic Review. JAMA 2009, 301:2362-2375.
• [29]Marik PE, Pastores SM, Annane D, Umberto Meduri G, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M: Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine. Critical Care Medicine 2008, 36:1937-1949.
• [30]Annane D, Maxime V, Ibrahim F, Alvarez JC, Abe E, Boudou P: Diagnosis of Adrenal Insufficiency in Severe Sepsis and Septic Shock. American Journal of Respiratory and Critical Care Medicine 2006, 174:1319-1326.
• [31]Reynolds SF, Heffner J: Airway management of the critically ill patient: rapid-sequence intubation. Chest 2005, 127:1397-1412.
• [32]Schenarts CL, Burton JH, Riker RR: Adrenocortical dysfunction following etomidate induction in emergency department patients. Acad Emerg Med 2001, 8:1-7.
• [33]Malerba G, Romano-Girard F, Cravoisy AL, Dousset B, Nace L, Levy B, Bollaert PE: Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med 2005, 31:388-392.
• [34]Albert SG, Ariyan S, Rather A: The effect of etomidate on adrenal function in critical illness: a systematic review. Intensive Care Med 2011, 37:901-910.